History Of Molecular Biology Research Articles

"Molecular Biology"-Pleonasm or Denotation for a Discipline of Its Own? Reflections on the Origins of Molecular Biology and Its Situation Today.

The disciplinary identity of molecular biology has frequently been called into question. Although the debates might sometimes have been more about creating or debunking myths, defending intellectual territory and the distribution of resources, there are interesting underlying questions about this area of biology and how it is conceptually organized. By looking at the history of molecular biology, its origins and development, I examine the possible criteria for its status as a scientific discipline. Doing so allows us to answer the title question in such a way that offers a reasonable middle ground, where molecular biology can be properly viewed as a viable interdisciplinary program that can very well be called a discipline in its own right, even if no strict boundaries can be established. In addition to this historical analysis, a couple of systematic issues from a philosophy of science perspective allow for some assessment of the current situation and the future of molecular biology.

Of Some Paradoxes in the Historiography of Molecular Biology.

Just when molecular biology is arguably delivering on some of its long-promised medical applications-think mRNA vaccines, monoclonal antibody drugs, PCR testing, and gene therapies-the history of molecular biology has lost much of its shine. What not too long ago seemed like a burgeoning field of research with endless possibilities, is now often reduced to the "central dogma" that saw its apotheosis in the effort to sequence the human genome but has since unraveled. The essay will discuss several possible answers to this apparent paradox.

The Black Box of Biology: A History of the Molecular Revolution. By Michel Morange; translated by Matthew Cobb. Cambridge (Massachusetts): Harvard University Press. $45.00. vi + 522 p.; index. ISBN: 9780674281363. [This volume is revised and expanded from the first English-language edition, published as A History of Molecular Biology.] 2020.

Previous articleNext article No AccessHistory, Philosophy, and Ethics of BiologyThe Black Box of Biology: A History of the Molecular Revolution. By Michel Morange; translated by Matthew Cobb. Cambridge (Massachusetts): Harvard University Press. $45.00. vi + 522 p.; index. ISBN: 9780674281363. [This volume is revised and expanded from the first English-language edition, published as A History of Molecular Biology.] 2020.Michael RuseMichael RuseProgram in History & Philosophy of Science, Florida State University, Tallahassee, Florida Search for more articles by this author PDFPDF PLUSFull Text Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by The Quarterly Review of Biology Volume 95, Number 4December 2020 Published in association with Stony Brook University Article DOIhttps://doi.org/10.1086/711808 Views: 56Total views on this site For permission to reuse, please contact [email protected]PDF download Crossref reports no articles citing this article.

Genome editing with the CRISPR-Cas system: an art, ethics and global regulatory perspective.

SummaryOver the last three decades, the development of new genome editing techniques, such as ODM, TALENs, ZFNs and the CRISPR‐Cas system, has led to significant progress in the field of plant and animal breeding. The CRISPR‐Cas system is the most versatile genome editing tool discovered in the history of molecular biology because it can be used to alter diverse genomes (e.g. genomes from both plants and animals) including human genomes with unprecedented ease, accuracy and high efficiency. The recent development and scope of CRISPR‐Cas system have raised new regulatory challenges around the world due to moral, ethical, safety and technical concerns associated with its applications in pre‐clinical and clinical research, biomedicine and agriculture. Here, we review the art, applications and potential risks of CRISPR‐Cas system in genome editing. We also highlight the patent and ethical issues of this technology along with regulatory frameworks established by various nations to regulate CRISPR‐Cas‐modified organisms/products.

For Want of a Template

For Want of a Template

The mechanistic-holistic divide revisited: The case of the lac operon

In this paper, I revisit the development of the repression model of genetic regulation in the lac operon to challenge a common application of a conceptual framework in the history of biology. I take Allen's (1978) account of the changes in the life sciences during the early and mid-twentieth century as an example of a common application of a framework based on the dichotomy between a mechanistic, or reductionist, approach to science and a holistic one. From this conceptual framework, Allen infers two general claims about the process of science and its goals: (1) that “mechanistic materialism” has often presented a more practical way to begin the study of complex phenomena in the life sciences, and (2) that the approach described as “holistic materialism” provides a more complete or accurate description of the natural world. The development of the lac operon model does not fit Allen's generalizations about scientific developments, and it can be used to cast some doubt on the scope of application of that conceptual framework. I argue that a better framework to interpret particular episodes in the history of molecular biology is to consider the ways in which biologists prioritize and track different aspects of the phenomena under study, rather than to focus on whether certain scientific practices are best described as developing from mechanistic to more holistic approaches. I end with some implications for the historiography of science by considering the appropriateness of different conceptual frameworks for different grains of resolution in the history of biology.

How planar are planar peptide bonds?

How planar are planar peptide bonds?

War and world of Erwin Chargaff (Dedicated to 110th anniversary of birth)

The article shortly describes the life path of Erwin Chargaff, one of the most famous figures in the history of molecular biology and genetics. Chargaff was born in Chernivtsi (Austria-Hungary, now Ukraine) but during the First World War his family was forced to move to Vienna. After graduating from the University of Vienna, Chargaff worked in Berlin, where he studied bacterial lipids. Due to Nazis coming to power in Germany, Chargaff moved to Paris and later (1935) emigrated to the USA and obtained a position at Columbia University, where he initially investigated the role of phospholipids in blood clotting. In 1944, applying novel methods Chargaff initiated intensive investigation of the chemical composition of nucleic acids from taxonomically distant species and established two rules which were later named after him. The first Chargaff's rule provided a significant support to Watson and Crick in construction of their double helical DNA model. The explosion of atomic bombs over Hiroshima and Nagasaki forced Chargaff to think about the moral responsibility of researchers and science to mankind. He begins to raise these issues in the press and manifests himself as a talented journalist, who criticized the bureaucratization of science and its transformation into a way of earning money. Despite decades of life in America, spiritually Erwin Chargaff always remained a European, who never forgot his roots and always remembered his native land.

Notes on Contributors

Notes on Contributors

Deep Reads: Strands in the History of Molecular Genetics

The history of molecular genetics, its precursors and descendants, is rich in events and colorful characters intertwining through the tumultuous history of the mid20th century. In this second iteration of ‘‘Deep Reads,’’ I try to trace selected strands in the ancestry of the field as told in histories, biographies, and memoirs, some of which I have, unlike Johnson, read through (Image 1). These recommendations form a tale of three successive intellectual utopias. In the first act, the precursors of molecular genetics take hold among physicists, in particular in those around Niels Bohr. In the second act, molecular genetics emerges in the 1940s, spreading out from the phage group and together with structural biology forming the nascent field of molecular biology. In the third act, a diaspora generation of geneticists applies the style of phage genetics to a menagerie of organisms: Caenorhabditis elegans, Drosophila, zebrafish, and Arabidopsis, among others. First though, for an epic and accessible history of molecular biology and genetics, I, like Jane Gitschier in the 2013 ‘‘Deep Reads,:Recommendations from Jane Gitschier9s Bookshelf ’’ return again to Horace Freeland Judson’s The Eighth Day of Creation (1979, expanded edition in 1996). I first read this as a teenager and remain captivated by Judson’s crisp, drama-filled accounts of discovery, based on countless interviews with the participants. As well as recounting the eureka moments, Judson also gives us the twists and turns, the blind alleys, and the failed experiments. A high point is the story of the maelstrom of experiment and theory that led to the deciphering of the genetic code (Part II, ‘‘RNA: The Functions of the Structure’’). If you read one book on the history of modern genetics, this has to be it!

Notes on Contributors

Notes on Contributors

Looking for quantum in life

The 1935 paper ‘‘On the Nature of Gene Mutation and Gene Structure’’ by Drosophila geneticist Nikolai Timofeeff-Ressovsky, radiation physicist Karl Gunter Zimmer, and theoretical physicist Max Delbruck (a student of the physicist Niels Bohr) has held an important place in the historiography of molecular biology. Commonly known as the ‘‘Three-Man Paper,’’ it has been situated at the center of the ‘‘origins’’ narrative in the history of molecular biology. In Phage and the Origins of Molecular Biology, the 1966 festschrift for one of the authors of the Three-Man Paper, Delbruck, some of his colleagues and disciples trace the birth of molecular biology to his attempt to discover ‘‘other laws of physics’’ through his study the phenomena of life and heredity: first he used biophysical methods, such as irradiation and quantum mechanics, to understand the stability of the gene; then he studied the phage, the hydrogen atom of biology, to ask fundamental questions about the nature of heredity. According to Erwin Schrodinger, his theoretical musings in What is Life? were inspired by the ThreeMan Paper, and his somewhat mythologized version of the Three-Man Paper in turn encouraged some physicists to shift their research on the problem of genetics. Indeed, self-proclaimed molecular biologists cherished the Three-Man Paper, suggesting that it exhibits some of the salient features of their discipline: its interdisciplinary approach to the problem of heredity, especially the applications of concepts of physics and of physical instruments; and its pursuit of a reductionist understanding of life based on the action of material genes. At long last, with the publication of Creating a Physical Biology: The Three-Man Paper and Early Molecular Biology, some of the key historical and philosophical issues underlying the Three-Man Paper have been eloquently told with a scholarly attention to analytic precision. First of all, the book offers the first English translation of the Three-Man Paper. Lucidly translated by Brandon Fogel, the Three-Man Paper has been often invoked for its historical and philosophical

Introduction to the Symposium on Synthetic Life

Introduction to the Symposium on Synthetic Life Alan N. Schechter, Editor On behalf of the editors of Perspectives in Biology and Medicine, I am pleased to introduce the editors and venue of the Symposium on Synthetic Life: Scientific, Historical, and Ethical Perspectives, which occupies much of the current issue of our journal. We are very pleased that Professors Ute Deichmann, Michel Morange, and Anthony S. Travis planned, organized, and edited the proceedings of the workshop on this topic, held on March 5-6, 2012, at the Jacques Loeb Centre for the History and Philosophy of the Life Sciences and the NIBN at Ben-Gurion University of the Negev in Beer Sheva, Israel. Professor Deichmann has been the founding director of the Centre since it was created in 2007. Although she trained in biology in Germany, most of her career has been devoted to the history of fundamental life science research during the last century, especially in Europe and including the dreadful periods before and during the Second World War. The Centre (as described in a bit more detail below) has become one of the few institutions in the world devoted to a systematic study of the transformations during the last century of those aspects of biology that might in their entirety be termed molecular biology. On the most general level, these transformations occurred in the context of the transition from the vague colloid theories at the beginning of the last century to analyses of specific molecules during the last several decades. Indeed, to understand the origins of molecular biology, and thus much of the current excitement in the life sciences and even medicine, one must know the several threads of structural and genetic analyses that came together as molecular biology in the mid-1950s and that have flourished since. It is the thesis of the symposium presented in the papers in this issue of Perspectives that further philosophical syntheses are now underway, including with synthetic chemistry to create the fields of synthetic biology and even synthetic life. This is analogous to the syntheses occurring with physiology that have led to what is generally termed systems biology. Professor Morange is Professor of Biology and Director of the Centre Cavaillès for history and philosophy of science at the Ecole Normale Supérieure in [End Page 467] Paris, and was trained initially in molecular biology. In the last two decades he has published several very well received books on the history of molecular biology, especially of the concept of genes, and on the history of science more generally. Professor Travis is interested in the history of chemistry and technology and has long been associated with the Sidney M. Edelstein Center for the History and Philosophy of Science, Technology and Medicine at the Hebrew University of Jerusalem, the Jacques Loeb Centre, and the Leo Baeck Institute in London. Thus the three editors bring very important and complementary perspectives to these issues. The Jacques Loeb Centre (http://in.bgu.ac.il/en/loeb/Pages/default.aspx) honors in its name the German-American physiologist who lived from 1859 to 1924 and from whom Professor Deichmann and her colleagues rightly trace the concepts that were the fundamental basis of the application of physical-chemical ideas and methods to biology during the last century. This work led to the complete replacement of the vitalistic approaches with the mechanistic tradition that we now accept with few second thoughts in fields ranging from evolution to medicine. In her writings, and in the focus of the work of the Centre, Professor Deichmann has traced the specific questions and controversies that constitute this history, including in the work of other pioneers, especially during the first half of the last century. Her paper on the contributions of Leonor Michaelis during this period is published as a special addition to this issue of Perspectives. The workshop proceedings published here are the fifth in a yearly series at the Centre. The titles of the others will give an idea of the scope of their enterprise: Philosophies in Biology (2008); Darwinism and Functional Biology, Other Sciences, and the Humanities (2009); Evolutionary-Developmental Biology: The Evolution of the Fields and Prospects for Future Developments (2010...

MicroRNAs and their role in gynecological tumors

There have been only few events in the history of molecular biology that could be compared to the discovery of microRNAs and their role in cell physiology and pathology. MicroRNAs are small, single-stranded, noncoding RNAs composed of 19-25 nucleotides (∼22 nt), which have been proven to regulate gene expression at the posttranscriptional level. The regulatory function of microRNAs was demonstrated in normal and diseased conditions. In particular, it has been linked to cell cycle regulation, cell proliferation and differentiation, inflammatory response, and apoptosis. Altered expression profiles of microRNA have been observed in many pathologies, including diabetes, rheumatoid arthritis, and several cancers. To date, more than 700 human microRNAs have been identified and in silico-based analyses estimate at least 500 more to be identified. The purpose of this review is to present the current perspective on microRNAs structure and biogenesis as well as their contribution to the etiopathogenesis of gynecological tumors. We discuss results of the recent publications that indicate possibilities of microRNAs use as novel markers for tumors screening, early diagnosis, and treatment monitoring. The possible utilization of microRNAs as prognostic factors and specific therapy targets is also reviewed.

Bacterial Exchange via Nanotubes: Lessons Learned from the History of Molecular Biology

DNA transfer between bacteria has a long and storied history. Starting shortly after the discovery by Avery, MacLeod, and McCarty that DNA was the genetic material, the exchange of DNA between bacteria confirmed that DNA transfer could stably change the phenotypic behavior of organisms. Continued effort along these lines led to the discovery of conjugation systems, bacteriophage transduction, bacterial genome mapping, and to some represents the birth of molecular biology. Recent findings by Dubey and Ben-Yehuda (2011) expand on these early results by suggesting that exchange between bacteria may occur continuously under certain growth conditions via nanotubes. These nanotubes have a structure similar to cell membranes and are sensitive to mild detergent treatment. Transfer of protein and plasmid DNA was demonstrated directly between neighboring and distant bacteria of the same and different genera. Transfer of RNA cannot be ruled out and the transfer of chromosomal DNA was not addressed. This work may reveal an important mechanism behind the spread of antibiotic resistance, however, much work remains to be done in order to confirm or refute the role of this mechanism in the dangerous spread of antibiotic resistance within the prokaryotic biosphere. The work of early molecular biology pioneers can be used as inspiration, if not as a direct template to guide future experimental confirmation.

The Paradox of the Phage Group: Essay Review

The 1966 festschrift for Max Delbriick, Phage and the Origins of Molecular Biology, effectively launched the history of molecular biol ogy, and it still echoes resoundingly in the historiography. Just three years after its appearance Delbriick shared the Nobel Prize in Physi ology or Medicine with Alfred Hershey and Salvador Luria "for their discoveries concerning 'the replication mechanism and the genetic structure of viruses.'"1 This volume of admiring essays was no doubt among the testimonials considered by the Caroline Institute of Medicine and its Nobel Committee.2 Gunther Stent's introduction to the collec tion, "Waiting for the Paradox," best articulates the book's underlying argument that the birth of molecular biology can be traced to Del briick's decision to study bacteriophage. As the standard view goes (in Stent's telling), physicists, disenchanted over the uses of the secrets of the atom for mass destruction, read Schrodinger's What is Life? as a vocational call to discover the secret of life.3 First among this band of physical scientists who would renovate biology was Delbriick, who had

Rethinking the Meaning of Biological Information

Throughout the history of molecular biology, the primary meaning of biological information has been taken from the image of a word-based linguistic code. I want to argue that the metaphor of such a code does not begin to capture either the variety or the richness of the processes by which nucleotide sequences inform biological processes. Current research demonstrates that nucleotide sequences inform not only development but also heredity and evolution, and they do so in all sorts of ways. Even though they do not exhaust the varieties of biological information employed in these processes, I claim that the power of DNA sequences to inform these processes is richer and perhaps far greater than the conventional understanding of genetic information permits, indeed richer than what any of our images of simple linguistic codes or of senders and receivers permits. Rather than a tape in a Turing machine or a message or signal sent through the generations, DNA is first and foremost a physicochemical structure with a range of potential uses by the physicochemical arsenal of biological cells that is so large as to expose the poverty of our most familiar metaphors. Recognition of this fact leads us to conclude that DNA is both more and less than we thought—more because it carries both symbolic and non-symbolic information and less because accepting that fact undermines its radical distinction from other biological molecules.

New wine in old bottles? The biotechnology problem in the history of molecular biology

This paper examines the “biotechnology problem” in the history of molecular biology, namely the alleged reinvention of a basic academic discipline looking for the logic of life, into a typical technoscientific enterprise, closely related to agriculture, medicine, and the construction of markets. The dominant STS model sees the roots of this shift in a radical change of the regime of knowledge production. The paper argues that this scheme needs to be historicized to take into account the past in our biotech present. Looking at the development of breast cancer genetic testing and GMOs as examples of mounting issues of intellectual property, risk and regulation, the paper also argues that historians of biology should pay closer attention to the political, the economical and the legal changes of the last thirty years. Solving the biotech problem requires new categories. The notion of “way of regulating” is given as an example of such notions linking the local and the global.

The Laboratory Technology of Discrete Molecular Separation: The Historical Development of Gel Electrophoresis and the Material Epistemology of Biomolecular Science, 1945–1970

Preparative and analytical methods developed by separation scientists have played an important role in the history of molecular biology. One such early method is gel electrophoresis, a technique that uses various types of gel as its supporting medium to separate charged molecules based on size and other properties. Historians of science, however, have only recently begun to pay closer attention to this material epistemological dimension of biomolecular science. This paper substantiates the historiographical thread that explores the relationship between modern laboratory practice and the production of scientific knowledge. It traces the historical development of gel electrophoresis from the mid-1940s to the mid-1960s, with careful attention to the interplay between technical developments and disciplinary shifts, especially the rise of molecular biology in this time-frame. Claiming that the early 1950s marked a decisive shift in the evolution of electrophoretic methods from moving boundary to zone electrophoresis, I reconstruct various trajectories in which scientists such as Oliver Smithies sought out the most desirable solid supporting medium for electrophoretic instrumentation. Biomolecular knowledge, I argue, emerged in part from this process of seeking the most appropriate supporting medium that allowed for discrete molecular separation and visualization. The early 1950s, therefore, marked not only an important turning point in the history of separation science, but also a transformative moment in the history of the life sciences as the growth of molecular biology depended in part on the epistemological access to the molecular realm available through these evolving technologies.

The Crux of Crucial Experiments: Duhem's Problems and Inference to the Best Explanation

Going back at least to Duhem, there is a tradition of thinking that crucial experiments are impossible in science. I analyse Duhem’s arguments and show that they are based on the excessively strong assumption that only deductive reasoning is permissible in experimental science. This opens the possibility that some principle of inductive inference could provide a sufficient reason for preferring one among a group of hypotheses on the basis of an appropriately controlled experiment. To be sure, there are analogues to Duhem’s problems that pertain to inductive inference. Using a famous experiment from the history of molecular biology as an example, I show that an experimentalist version of inference to the best explanation (IBE) does a better job in handling these problems than other accounts of scientific inference. Furthermore, I introduce a concept of experimental mechanism and show that it can guide inferences from data within an IBE-based framework for induction.